Erythropoietin ameliorates early ischemia-reperfusion injury following the Pringle maneuver

AIM:To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM),in comparison with conventional steroid administration in a prospective randomized trial. METHODS:Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups:(1) A steroid group (STRD, n= 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2) An EPO1 group (n=10) who received 30 000 U of Epo before the PM and at the end of surgery; and (3) An EPO2 group (n=8) who received 60 000 U of Epo before the PM. Hemoglobin (Hb), hematocrit (Ht), aspartate aminotransferase (AST), alanine transaminase (ALT),lactate dehydrogenase (LDH), lactate, interleukin-6 (IL-6),and tumor necrosis factor(TNF)-α were measured before and just after (Day 0) surgery, and on postoperative days 1, 3, 7 and 14. RESULTS: There were no increases in Hb and Ht in the EPO1 and EPO2 groups. AST was signif icantly lower in EPO1 than in STRD on Day 0 (P=0.041), and lower in EPO1 than in STRD and EPO2 on Day 1 (P=0.018). ALT was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.020) and Day 1 (P=0.004). There were no signif icant inter-group differences in the levels of LDH and lactate. IL-6 was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0036) and Day 1 (P=0.0451). TNF-α was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0006) and Day 1 (P<0.0001). Furthermore, hospitalization was signif icantly shorter in EPO1 and EPO2 than in STRD.CONCLUSION:Epo has greater potential than steroids to ameliorate IR/I after the PM. Epo at a dose of 30000 U, administered before PM and just after surgery, yields better results.

Liver resections can be performed safely without Pringle maneuver: A prospective study

AIM To evaluate liver resections without Pringle maneuver, i.e., clamping of the portal triad. METHODS Between 9/2002 and 7/2013, 175 consecutive liver resections(n = 101 major anatomical and n = 74 large atypical > 5 cm) without Pringle maneuver were performed in 127 patients(143 surgeries). Accompanying, 37 wedge resections(specimens < 5 cm) and 43 radiofrequency ablations were performed. Preoperative volumetric calculation of the liver remnant preceeded all anatomical resections. The liver parenchyma was dissected by waterjet. The median central venous pressure was 4 mmH g(range: 5-14). Data was collected prospectively. RESULTS The median age of patients was 60 years(range: 16-85). Preoperative chemotherapy was used in 70 cases(49.0%). Liver cirrhosis was present in 6.3%, and liver steatosis of ≥ 10% in 28.0%. Blood loss was median 400 mL(range 50-5000 mL). Perioperative blood transfusions were given in 22/143 procedures(15%). The median weight of anatomically resected liver specimens was 525 g(range: 51-1850 g). One patient died postoperatively. Biliary leakages(n = 5) were treated conservatively. Temporary liver failure occurred in two patients.CONCLUSION Major liver resections without Pringle maneuver are feasible and safe. The avoidance of liver inflow clamping might reduce liver damage and failure, and shorten the hospital stay.

Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

BACKGROUND The Pringle maneuver[portal triad obstruction(PTO)]provides huge disturbances during ischemia and even more thereafter in reperfusion.Contrarily,a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion conditions.Recently,BPC 157,as a cytoprotective agent,successfully resolved vessel occlusions in rats(ischemic colitis;deep vein thrombosis,superior anterior pancreaticoduodenal vein;bile duct cirrhosis)through rapid collateral vessel recruitment to circumvent vessel occlusion.Thereby,medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively,at various time points during reperfusion.AIM To introduce BPC 157 therapy against pringle maneuver-damage.METHODS In deeply anesthetised rats,the portal triad was clamped up for 30 min.Rats then underwent reperfusion for either 15 min or 24 h.Medication[(10μg,10 ng/kg)regimens,administered as a single challenge]picked(a)ischemia,PTO period[at 5 min before(ip)or at 5 or 30 min of ligation time(as a bath to PTO)]or(b)reperfusion,post-PTO period[at 1 or 15 min(bath during surgery)or 24 h(ip)reperfusion-time].We provided gross,microscopy,malondialdehyde,serum enzymes,electrocardiogram,portal,caval,and aortal pressure,thrombosis and venography assessments.RESULTS BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude,S1Q3T3 QRS pattern and tachycardia).Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein)as the adequate shunting immediately affected disturbed haemodynamics.Portal hypertension and severe aortal hypotension during PTO,as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO)or completely abrogated(reperfusion);thrombosis in portal vein tributaries and inferior caval vein or hepatic artery was counteracted during portal triad obstruction PTO.Also,counteraction included the whole vicious injurious circle[i.e.,lung pathology(severe capillary congestion),liver(dilated central veins and terminal portal venules),intestine(substantial capillary congestion,submucosal oedema,loss of villous architecture),splenomegaly,right heart(picked P wave values)]regularly perpetuated in ischemia and progressed by reperfusion in Pringle rats.CONCLUSION BPC 157 resolves pringle maneuver-damage in rats,both for ischemia and reperfusion.

Gastric pentadecapeptide BPC 157 in cytoprotection to resolve major vessel occlusion disturbances,ischemia-reperfusion injury following Pringle maneuver,and Budd-Chiari syndrome

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 therapy.Conceptually,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow.In this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky syndrome.As a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO pathways.In the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain axis.As the time went on,with its reported effects,it is likely most useful theory practical implementation and justification.Meantime,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis trials.Likely,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects.

Hepatic blood inflow occlusion with/without hemihepatic artery control versus the Pringle maneuver in resection of hepatocellular carcinoma： a retrospective comparative analysis

Background The Pringle maneuver, which has been the standard for hepatic resection surgery for a long time, has the major flaw of ischemic damage in the liver. The aim of this research was to evaluate hepatic blood inflow occlusion with/without hemihepatic artery control vs. the Pringle maneuver in hepatocellular carcinoma （HCC） resection. Methods Two hundred and eighty-one cases of resection of HCC with hepatic blood inflow occlusion （with/without hemihepatic artery control） and the Pringle maneuver from January 2006 to December 2008 in our hospital were analyzed and compared retrospectively; among them 107 were in group I （Pringle maneuver）, 98 in group II （hepatic blood inflow occlusion）, and 76 in group III （hepatic blood inflow occlusion without hemihepatic artery control）. The operation time, intraoperative blood loss, postoperative liver function and complications were used as the endpoints for evaluation. Results The operative duration and intraoperative blood loss of three groups showed no significant difference; alanine aminotransferase, total bilirubin and incidence of postoperative complications were significantly lower in groups II and Ill postoperation than those in group I. Conclusion Hepatic blood inflow occlusion without hemihepatic artery control is safe, convenient and feasible for resection of HCC, especially for cases involving underlying diseases such as cirrhosis.

Methods of vascular control technique during liver resection:a comprehensive review

BACKGROUND: Significant hemorrhage together with blood transfusion increases postoperative morbidity and mortality of hepatic resection. Hepatic vascular occlusion is effective in minimizing bleeding during hepatic parenchymal transection. This article aimed to review the current role and status of various techniques of hepatic vascular occlusion during hepatic resection. DATA SOURCES: The relevant manuscripts were identified by searching MEDLINE, and PubMed for articles published between January 1980 and April 2010 using the keywords 'vascular control', 'vascular clamping', 'vascular exclusion' and 'hepatectomy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: One randomized controlled trial (RCT) and 5 RCTs showed intermittent Pringle maneuver and ischemic preconditioning followed by continuous Pringle maneuver were superior to continuous Pringle maneuver alone, respectively. Two RCTs compared the outcomes of hepatectomy with and without intermittent Pringle maneuver. One showed Pringle maneuver to be beneficial, while the other failed to show any benefit. One RCT showed that ischemic preconditioning had significantly less blood loss than using intermittent Pringle maneuver. Four RCTs evaluated the use of hemihepatic vascular occlusion. One RCT showed it had significantly less blood loss than Pringle maneuver, while the other 3 showed no significant difference. Only 1 RCT showed it had significantly less liver ischemic injury. No RCT had been carried out to assess segmental vascular occlusion. Two RCTs compared the outcomes of total hepatic vascular exclusion (THVE) and Pringle maneuver. One RCT showed THVE resulted in similar blood loss, but a higher postoperative complication. The other RCT showed less blood loss using THVE but the postoperative complication rate was similar. Both studies showed similar degree of liver ischemic injury. Only one RCT showed that selective hepatic vascular exclusion (SHVE) had less blood loss and liver ischemic injury than Pringle maneuver. CONCLUSION: Due to the great variations in these studies, it is difficult to draw a definitive conclusion on the best technique of hepatic vascular control.

Radiofrequency ablation-assisted liver resection a step toward bloodless liver resection

BACKGROUND： Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver resection.METHODS： A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated.RESULTS： Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 m L, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients（8.3%）. The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients（32.4%） with postoperative complications. There is no mortality within 30 days after surgery. CONCLUSIONS： Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality.